crossing96/oncoscreening huggingface dataset:
Intravesical Toll-like receptor 7 agonist R-837: optimization of its formulation in an orthotopic mouse model of bladder cancer.	OBJECTIVE: To study the immune response caused by the intravesical administration of the immunomodulator R-837 in various formulations and to estimate its therapeutic potential for bladder cancer. METHODS: Female C57BL/6 mice were intravesically treated with different formulations of R-837, a Toll-like receptor 7 agonist used for treating genital warts and skin malignancy. The tested formulation mixtures contained different ratios of lactic acid, a thermosensitive poloxamer polymer (Lutrol F127) and 2-(hydroxypropyl)-beta-cyclodextrin (HPbetaCD). Induction of tumor necrosis factor alpha (TNFalpha) and keratinocyte-derived chemokine (KC) was analyzed by Luminex microbeads assay. The therapeutic potential of intravesical administration of R-837 was assessed in an orthotopic, syngeneic mouse model of bladder cancer using MB49 cells. RESULTS: Intravesical administration of R-837 in lactic acid alone induced systemic and bladder TNFalpha and KC in a dose-dependent manner. Formulations including poloxamer decreased systemic absorption of R-837 and significantly reduced systemic and local induction of KC. Addition of HPbetaCD in the poloxamer formulation particularly reversed levels of systemic and local levels of TNFalpha and KC. Histological examination showed that poloxamer-HPbetaCD formulation allowed infiltration of mononuclear cells into urothelium and lamina propria. In studies using orthotopic mouse bladder cancer, the tumor loads in R-837-treated mice were significantly lower than those in vehicle-treated or non-treated mice. CONCLUSION: The optimized poloxamer-HPbetaCD formulation of R-837 shows therapeutic potential for bladder cancer while avoiding adverse side-effects.	bladder
Maspin modulates adhesion of bladder carcinoma cells to vascular endothelium.	PURPOSE: Maspin belongs to the serpin family and has been shown to suppress tumor growth and metastasis in several tumor types. The role of maspin in bladder carcinoma has not been fully elucidated, and the object of this study was to investigate whether maspin contributes to bladder tumor adhesion to vascular endothelial cells (HUVEC). METHODS: Expression of maspin-coding mRNA was evaluated in a panel of bladder carcinoma cell lines. Maspin distribution in maspin mRNA(high) versus maspin mRNA(low) cells was further analyzed by flow cytometry and confocal microscopy. Adhesion to HUVEC was measured in a coculture model and correlated with the surface-bound maspin. RESULTS: Maspin(high) (RT-4, RT-112) cell lines strongly attached to HUVEC, whereas maspin(low) (UMUC-3, MGH-U1) cell lines poorly adhered to HUVEC. Distinct cytoplasmic maspin accumulation and moderate surface-bound maspin was found in RT-4 cells. Blocking maspin surface receptors prevented tumor cell attachment to HUVEC, indicating that surface-bound maspin is responsible for triggering cell adhesion. PMA-triggered elevation of surface-bound maspin was accompanied by an enhanced adhesion capacity of RT-4 cells, compared to controls. Finally, exposing the bladder carcinoma cells to the differentiation-inducing agent valproic acid led to a surface-bound (but not cytoplasmic) maspin decrease, paralleled by a significant reduction in tumor cell binding to HUVEC. CONCLUSION: Surface-bound maspin directly controls bladder carcinoma cell adhesion to the vascular wall. Blocking this process may prevent transendothelial migration and tumor cell dissemination. Therefore, therapeutic down-regulation of surface-bound maspin might become an option to prevent tumor spread into distant organs.	bladder
Characteristics and outcomes of patients with clinical carcinoma in situ only treated with radical cystectomy: an international study of 243 patients.	PURPOSE: We describe the rate of up staging and the cancer specific outcomes of patients with carcinoma in situ refractory to transurethral resection with intravesical therapy treated with radical cystectomy. MATERIALS AND METHODS: The records of 3,207 patients treated with radical cystectomy for urothelial carcinoma of the bladder at 8 centers in the United States, Canada and Europe were reviewed. RESULTS: Of the 3,207 patients who underwent radical cystectomy 243 (7.6%) had clinical carcinoma in situ only disease before radical cystectomy. At radical cystectomy 117 patients (48.1%) had carcinoma in situ only, 20 (8.2%) had pT0 urothelial carcinoma of the bladder, 19 (7.8%) had pTa urothelial carcinoma of the bladder and 36% had disease up staged (32 [13.2%] pT1, 29 [11.9%] pT2, 12 [4.9%] pT3 and 14 [5.8%] pT4). A total of 22 patients (9.1%) had lymphovascular invasion in the radical cystectomy specimen and 14 (5.8%) had metastasis to regional lymph nodes. Overall 5-year recurrence-free and cancer specific survival estimates were 74% (95% CI 68-79) and 85% (95% CI 80-89), respectively. On multivariable analysis adjusting for the effects of standard predictors, lymph node metastasis and lymphovascular invasion were associated with an increased risk of disease recurrence (p = 0.017 and p = 0.043, respectively) and cancer specific mortality (p = 0.019 and p = 0.001, respectively). Female gender was an independent risk factor for cancer specific mortality (p = 0.029) but not for disease recurrence (p = 0.173). CONCLUSIONS: Approximately a fourth of patients treated with radical cystectomy for clinical carcinoma in situ only had muscle invasive disease and 5.8% had metastasis to regional lymph nodes. Identification of those patients with a potentially aggressive natural history of carcinoma in situ is of the utmost importance as they are likely to benefit from early radical cystectomy.	bladder
A report of iliac muscle abscess due to Mycobacterium bovis after bacillus Calmette-Guerin therapy for bladder cancer.	Bacillus Calmette-Guerin (BCG) vaccine is traditionally used for vaccination against tuberculosis. BCG vaccine contains live attenuated strain of Mycobacterium bovis. Intravesical BCG is also effective in treatment of transitional cell carcinoma of the urinary bladder. Complications after intravesical BCG immunotherapy are extremely rare. We report an iliac muscle abscess due to M bovis that developed 4 years after intravesical BCG therapy for bladder cancer. Infection with M bovis, though rare, should be considered in patients with prior BCG therapy for bladder cancer.	bladder
[De novo urological neoplasms in kidney transplant patients: experience in 1,751 patients].	INTRODUCTION: Immunosuppressive treatment promotes development of neoplasms in kidney transplant patients. Cancer prevalence in these patients is 4 to 5 times higher as compared to the general population. Tumors are also known to behave more aggressively in transplant patients. OBJECTIVE: To perform a descriptive analysis of de novo urological tumors in kidney transplant patients and to analyze patient survival. MATERIALS AND METHODS: A retrospective study was conducted in 1751 transplant patients from January 1980 to December 2006. Patients in whom the tumor occurred in the first year after transplantation were excluded. The primary variables considered included sex, age at transplant, age at cancer diagnosis, site, clinical stage, treatment, and outcome. A Chi-square test was used for univariate statistical analysis. Survival was assessed using the Kaplan-Meier method. RESULTS: Twenty-nine de novo tumors (1.6%) were diagnosed in the 1751 transplanted patients, with a median follow-up of 35.28 months (2-121) from tumor diagnosis. Tumors were found in 24 males (82%) and 5 females (18%). Median age at transplantation was 50.8 (17-70) years, and median age at tumor diagnosis was 56.4 (19-79) years. Eleven patients (38%) were diagnosed with prostate cancer, seven (24%) with bladder tumors, 4 (60%) with non-muscle invasive tumors, and 3 (40%) with muscle invasive tumors. A renal adenocarcinoma in the primitive kidney was diagnosed in 6 patients (20%). Five patients (18%) were detected a tumor in the transplanted kidney. Median survival was 75 months for patients with bladder tumors, 82 months for prostate cancer, 59 months for tumors in the native kidney, and 86 months for graft tumors. CONCLUSIONS: In our series, de novo urological tumors in kidney transplant recipients were more common in males. Prostate cancer is the most common tumor and renal cell carcinoma of the native kidney has the worst survival rate.	bladder
[Update of the Clinical Guidelines of the European Association of Urology on muscle-invasive and metastatic bladder carcinoma].	CONTEXT: New data regarding diagnosis and treatment of muscle-invasive and metastatic bladder cancer (MiM-BC) has emerged and led to an update of the European Association of Urology (EAU) guidelines for MiM-BC. OBJECTIVE: To review the new EAU guidelines for MiM-BC. EVIDENCE ACQUISITION: A comprehensive workup of the literature obtained from Medline, the Cochrane central register of systematic reviews, and reference lists in publications and review articles was developed and screened by a group of urologists, oncologists, and radiologist appointed by the EAU Guideline Committee. Previous recommendations based on the older literature on this subject were taken into account. Levels of evidence and grade of guideline recommendations were added, modified from the Oxford Centre for Evidence-based Medicine Levels of Evidence. EVIDENCE SYNTHESIS: The diagnosis of muscle-invasive bladder cancer (BCa) is made by transurethral resection (TUR) and following histopathologic evaluation. Patients with confirmed muscle-invasive BCa should be staged by computed tomography (CT) scans of the chest, abdomen, and pelvis, if available. Adjuvant chemotherapy is currently only advised within clinical trials. Radical cystectomy (RC) is the treatment of choice for both sexes, and lymph node dissection should be an integral part of cystectomy. An orthotopic bladder substitute should be offered to both male and female patients lacking any contraindications, such as no tumour at the level of urethral dissection. Multimodality bladder-preserving treatment in localised disease is currently regarded only as an alternative in selected, well-informed, and compliant patients for whom cystectomy is not considered for clinical or personal reasons. An appropriate schedule for disease monitoring should be based on: a) natural timing of recurrence; b) probability of disease recurrence; c) functional deterioration at particular sites; and d) consideration of treatment of a recurrence. In metastatic disease, the first-line treatment for patients fit enough to sustain cisplatin is cisplatin-containing combination chemotherapy. Presently, there is no standard second-line chemotherapy. CONCLUSIONS: These EAU guidelines are a short, comprehensive overview of the updated guidelines of (MiM-BC) as recently published in the EAU guidelines and also available in the National Guideline Clearinghouse.	bladder
Empirical receiver operating characteristic curve for two-sample comparison with cure fractions.	"Two-sample comparison of survival times with ""cured patients"" is of major interest and a challenging issue in many areas, particularly in cancer clinical research. Recently, several authors have proposed various procedures of comparison, including tests of no overall, no short-term and no long-term differences between two samples. In clinical practice, it is often of interest to detect the difference in treatment effects among noncured patients regardless of the difference between cure fractions. In this paper, we propose a statistical test to compare two samples with cured patients and possibly heterogeneous treatment effects based on a class of semi-parametric transformation models, and our main focus is on the survival times of noncured patients. The empirical and quantile processes are used to construct strong approximations for the empirical curves. The two-sample test is then constructed from general least squares estimators derived from these processes. Simulation results show that the proposed test perform well. As an example of application, a set of bladder cancer data is analyzed to illustrate the proposed methods."	bladder
Robot-assisted laparoscopic cystoprostatectomy with extended pelvic lymphadenectomy, extracorporeal enterocystoplasty, and intracorporeal enterourethral anastomosis: initial Montsouris experience.	BACKGROUND AND PURPOSE: Radical cystectomy is the gold standard for management of invasive and recurrent high-grade superficial bladder cancer. We present our initial experience with robot-assisted laparoscopic cystoprostatectomy (RALCP) with extended pelvic lymphadenectomy (epLAD) and intracorporeal enterourethral anastomosis (IEUA). A video demonstrating our technique is available online at www.liebertonline.com/end. PATIENTS AND METHODS: Between April 2008 and March 2009, nine patients underwent RALCP with epLAD and IEUA at our institution. Operative technique, as described in detail (with video), was assessed for feasibility. A video demonstrating this technique is available online at www.liebertonline.com/end. Preoperative patient characteristics, operative data, as well as perioperative and pathologic outcomes were analyzed. All data were collected prospectively. RESULTS: Median total operative time was 270 minutes (range 210-330): 60 minutes, bilateral epLAD; 90 minutes, RALCP; 60 minutes, open enterocystoplasty; 60 minutes (range 45-90), IEUA. Median blood loss was 400 mL (range 200-900 mL). All surgical margins were negative. Median number of lymph nodes removed was 11 (range 4-21). Postoperative complications were noted in three patients and included urinoma (n = 1), pyelonephritis (n = 1), and hematoma (n = 1). CONCLUSION: RALCP is feasible and can be performed safely and effectively with acceptable operative, pathologic, and short-term clinical outcomes. More experience with longer follow-up is necessary to further assess clinical and oncologic outcomes of robotic assisted laparoscopic cystectomy for treatment of bladder cancer.	bladder
Role of anti-Her-2 therapy in bladder carcinoma.	Bladder cancer, in its advanced stage, has very few therapeutic strategies with proven efficacy. Platinum-combination chemotherapy can be considered a standard for first-line therapy, but after progression there is no standard therapy, and the prognosis is very poor. The development of targeted therapies in the last few years has significantly changed the prognosis of a wide variety of tumors. In bladder cancer, there is no targeted therapy currently approved for its use in advanced disease. There is evidence that Her-2 amplification and/or overexpression is seen in bladder cancer, and may influence prognosis. Anti-Her-2 drugs, such as trastuzumab or lapatinib, are under investigation in urothelial neoplasms, but there is no phase III trial that has evaluated their use in bladder cancer. We review the published evidence about Her-2 determination, its influence on bladder carcinoma prognosis, the clinical development of anti-Her-2-targeted therapies, and the possible future research directions involving this pathway in bladder cancer.	bladder
Immunostimulatory effects of extract of Pulicaria crispa before and after Schistosoma mansoni infection.	The immunostimulatory effects of methanolic extract from Pulicaria crispa were investigated in mice before and after infection with Schistosoma mansoni. Mice were subjected for daily intra-peritoneal injection by the extract (33 ng/mouse) for 10 successive days followed by infecting every mouse with 100 S. mansoni cercariae. Treatment with the extract induced significant increase (p < 0.05) in sera-IL-2 before and after infection. Upon using soluble worm antigen preparation or cancer bladder homogenates as antigens in ELISA, the detected levels of IgG were significantly (p < 0.05) higher in sera from treated-infected mice than untreated P. crispa infected mice. Using crude Escherichia coli lysate as an antigen in ELISA, it was detected a significant (p < 0.05) increase in IgG levels in sera from the extract-treated mice before and after infection.	bladder
Robot-assisted radical cystectomy: an expert panel review of the current status and future direction.	OBJECTIVE: At the 9th Annual Meeting of the Society of Urologic Oncology (SUO), an expert panel discussed the current status of robot-assisted radical cystectomy (RARC). MATERIALS AND METHODS: The presentations were derived from: (1) review of published literature, unpublished addendums, and SUO abstracts, (2) initial abstract data of pooled results of 528 patients from the International Robot-Assisted Cystectomy Consortium (IRCC), and (3) an internet-based survey of the SUO membership (n = 54) on training and practice patterns related to RARC. RESULTS: Using pathologic assessment of surgical margins as a surrogate for cancer control, the results are favorable with organ confined disease, with select expert series showing no positive margins and the IRCC group reporting 4%. In non-organ-confined disease, select expert series also show no positive margins, while for the IRCC group it was 15%. The median lymph node yield in all series is 12-19 with 5%-33% positive. The S-model robot is preferred for an extended node dissection to the aortic bifurcation. In experienced hands, estimated blood loss is <500 cc, and hospital discharge by postoperative d 4-5. Complications appear similar to open and decrease with experience. In one study comparing RARC to open, pain scales were similar but morphine use was consistently lower for RARC. The technique is most often applied to the bladder and lymph nodes only with a mini-laparotomy for the diversion; technical considerations for female patients were described. The membership surveys showed that 37% of respondents have attempted RARC, but < 20% received robot console training during fellowship. The greatest area of concern was the adequacy of the lymph node dissection in the higher regions--common iliac to peri-caval/aortic. CONCLUSIONS: Initial reports of RARC demonstrate feasibility of technique, early oncologic outcomes, and learning curve experiences. Surgeons learning RARC should select patients without clinical evidence of locally advanced disease, and consider a second look open node dissection. Experienced surgeons have demonstrated the possibility of reduced blood loss, opiate requirement, and hospital stay. Moving forward, an international consortium has been organized to address the unmet needs of prospective comparisons with long-term oncologic outcomes, standardized complication reporting, and quality of life.	bladder
Functional significance of the hepaCAM gene in bladder cancer.	BACKGROUND: The hepaCAM gene encodes a new immunoglobulin-like cell adhesion molecule, and its expression is suppressed in a variety of human cancers. Additionally, hepaCAM possesses properties often observed in tumor suppressor genes. However, the expression and biological function of hepaCAM has not been investigated in bladder cancer. Therefore we sought to examine hepaCAM expression and the relationship between its structure and function in human transitional cell carcinoma of bladder (TCCB). MATERIALS AND METHODS: HepaCAM expression was evaluated in 28 normal and 34 TCCB bladder specimens and 2 TCCB cell lines using semi-quantitative RT-PCR. The wild-type hepaCAM and the extracellular domain-truncated mutant gene were transfected into the TCCB cell line T24, and the biological properties of both the wild-type gene and the domain-truncated mutant were then assessed. RESULTS: HepaCAM expression was down-regulated in 82% (28/34) of TCCB specimens and undetectable in the 2 TCCB cell lines tested. The localization of hepaCAM appeared to be dependent on cell density in T24 cells. In widely spread cells, hepaCAM accumulated on the perinuclear membrane and the cell surface protrusions, whereas in confluent cells, hepaCAM was predominantly localized at the sites of cell-cell contacts on the cell membrane. Functionally, hepaCAM expressed not only increased cell spreading, delayed cell detachment, enhanced wound healing and increased cell invasion; it also inhibited cell growth (P < 0.01). When the extracellular domain was deleted, the localization of hepaCAM was significantly altered, and it lost both its adhesive function and its influence on cell growth. CONCLUSIONS: HepaCAM is involved in cell adhesion and growth control, and its expression is frequently silenced in TCCB. The extracellular domain of hepaCAM is essential to its physiological and biological functions.	bladder
The prognostic value of cadherin switch in bladder cancer.	Loss of E-cadherin expression and gain of N-cadherin expression ('cadherin switch') is shown to be characteristic in epithelial to mesenchymal transition (EMT), a mechanism associated with cancer progression. Furthermore, the prognostic role of P-cadherin in different cancers is controversial. The aim of this study was to evaluate the prognostic significance of 'cadherin switch' on the gene expression level in bladder cancer. Frozen tissue samples of 181 bladder cancer patients and 7 control individuals were analyzed by quantitative real-time PCR. Kaplan-Meier log-rank test and Cox univariate and multivariate analysis were performed to assess the prognostic relevance of gene expression of E-, N- and P-cadherin. Cox univariate analysis revealed that the decrease of E-cadherin and the gain of N-cadherin gene expression are risk factors for cancer-related death (P=0.087, P=0.005, respectively). Fourteen percent (13/92) of muscle-invasive bladder cancers were N-cadherin- negative. These patients had a significantly poorer prognosis than those with N-cadherin-positive muscle-invasive tumors (P=0.024). P-cadherin gene expression proved to be a significant independent prognostic factor for both cancer-specific and recurrence-free survival (P=0.011, P=0.036). The characteristic 'cadherin switch' between low- and high-stage tumors that we observed and the prognostic significance of E-, N- and P-cadherin suggests the importance of these markers in bladder cancer progression. The poor patient prognosis in N-cadherin-negative muscle-invasive tumors indicates an alternative, N-cadherin-independent way in bladder cancer progression.	bladder
Failure of bacille Calmette-Guérin in patients with high risk non-muscle-invasive bladder cancer unsuitable for radical cystectomy: an update of available treatment options.	Although the accepted standard upon failing intravesical bacille Calmette-Guérin (BCG) in patients with high-risk non-muscle-invasive bladder cancer (NMIBC) is radical cystectomy, there are some patients for whom this is not an option. We critically reviewed previous reports on the treatment possibilities available in such a clinical scenario. The options available can be categorized as chemotherapy, immunotherapy, device-assisted therapy and combined therapy. Combining new with established intravesical treatments seems to hold the most promise. Maintenance thermo-chemotherapy gives a reported 2-year disease-free survival rate of 50% and in small early-phase studies of intravesical gemcitabine administered in combination with mitomycin-C, tolerance and efficacy data would suggest the need for larger trials, given the early encouraging results. Electromotive mitomycin-C given sequentially with BCG might not only reduce the recurrence rate but also reduce progression and disease-specific mortality, although currently there is no trial in a specific population with 'BCG failure'.	bladder
Radiation dose-volume effects of the urinary bladder.	An in-depth overview of the normal-tissue radiation tolerance of the urinary bladder is presented. The most informative studies consider whole-organ irradiation. The data on partial-organ/nonuniform irradiation are suspect because the bladder motion is not accounted for, and many studies lack long enough follow-up data. Future studies are needed.	bladder